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US 6,284,766 B1Granted
9H-pyrimido [4,5-b] indole derivatives: CRF1 specific ligands
AssigneeNeurogen Corporation
InventorRaymond F. Horvath
Life of this patent
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Abstract
Disclosed are compounds of the formula: wherein Ar, R1, R2, R3, R4 and R5 are defined herein, which compounds are selective antagonists at CRF1 receptors and are therefore useful in the diagnosis and treatment of stress related disorders such as post traumatic stress disorder (PTSD) as well as depression, headache, anxiety, cardiovascular disorders, and eating disorders. Methods of treatment of such disorders and well as packaged pharmaceutical compositions are also disclosed.
Claims13
A compound of the formula:
- or a pharmaceutically acceptable salt thereof wherein
- Ar is phenyl, 1- or 2-naphthyl, 2-, 3-, or 4-pyridyl, 2-, 4- or 5-pyrimidinyl, each of which is mono-, di-, or trisubstituted with halogen, trifluoromethyl, hydroxy, amino, cyano, carboxamide, C1-C6 alkyl, C1-C6 alkoxy, C3-C7 cycloalkyl, or amino(C1-C6)alkyl with the proviso that at least one of the ortho or para positions of Ar is substituted;
- R1 is hydrogen, halogen, trifluoromethyl, carboxamide, carboxylate, C1-C6 alkyl, C3-C7 cycloalkyl, or (C1-C6 alkyl)-G1—R6 wherein G1 is nitrogen, oxygen or sulfur and R6 is hydrogen, C3-C7 cycloalkyl, or C1-C6 alkyl;
- R2 and R3 are taken together, and represent —CH═A—CH═CH—, wherein
- A is CR8;
- R8 is —NR9R9′;
- and
- R9 and R9′ independently represent hydrogen or (C1-C6)alkyl;
- R4 and R5 are the same or different and represent hydrogen hydroxy, C1-C6 alkoxy(C1-C6)alkyl, hydroxy(C1-C6)alkyl, C3-C7 cycloalkyl, or C1-C6 alkyl;
- or
- phenyl, 2-, 3-, or 4-pyridyl, 2- or 3-thienyl, or 2-, 4-, or 5-pyrimidinyl, each of which is optionally mono- or disubstituted with halogen, hydroxy, C1-C6 alkyl, C3-C7 cycloalkyl, or C1-C6 alkoxy;
- or
- R4 and R5 together represent —(C2-C3)—G3—(C1-C3)— where
- G3 is methylene, 1,2 phenylene, oxygen, sulfur or NR10;
- and
- R10 is C1-C6 alkyl, C3-C7 cycloalkyl, phenyl, 2-, 3-, or 4-pyridyl, 2- or 3-thienyl, or 2-, 4- or 5-pyrimidyl.
13 more elements
A compound of the formula:
- or a pharmaceutically acceptable salt thereof wherein
- Ar is phenyl, 1- or 2-naphthyl, 2-, 3-, or 4-pyridyl, 2-, 4- or 5-pyrimidinyl, each of which is mono-, di-, or trisubstituted with halogen, trifluoromethyl, hydroxy, amino, cyano, carboxamide, C1-C6 alkyl, C1-C6 alkoxy, C3-C7 cycloalkyl, or amino(C1-C6)alkyl with the proviso that at least one of the ortho or para positions of Ar is substituted;
- R1 is hydrogen, halogen, trifluoromethyl, carboxamide, carboxylate, C1-C6 alkyl, C3-C7 cycloalkyl, or (C1-C6 alkyl)-G1—R6 wherein G1 is nitrogen, oxygen or sulfur and R6 is hydrogen, C3-C7 cycloalkyl, or C1-C6 alkyl;
- R2 and R3 are taken together, and represent —CH═A—CH═CH—, wherein
- A is CR8;
- R8 is —(C1-C6 alkyl)-NR9R9′;
- and
- R9 and R9′ independently represent hydrogen or (C1-C6)alkyl;
- R4 and R5 are the same or different and represent hydrogen hydroxy, C1-C6 alkoxy(C1-C6)alkyl, hydroxy(C1-C6)alkyl, C3-C7 cycloalkyl, or C1-C6 alkyl;
- or
- phenyl, 2-, 3-, or 4-pyridyl, 2- or 3-thienyl, or 2-, 4-, or 5-pyrimidinyl, each of which is optionally mono- or disubstituted with halogen, hydroxy, C1-C6 alkyl, C3-C7 cycloalkyl, or C1-C6 alkoxy;
- or
- R4 and R5 together represent —(C2-C3)—G3—(C1-C3)— where
- G3 is methylene, 1,2 phenylene, oxygen, sulfur or NR10;
- and
- R10 is C1-C6 alkyl, C3-C7 cycloalkyl, phenyl, 2-, 3-, or 4-pyridyl, 2- or 3-thienyl, or 2-, 4- or 5-pyrimidyl.
13 more elements
Dependencies are inferred from the claim text.